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Biomedical subjects

M F Marmor

Publications and source records attributed to M F Marmor.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pattern dystrophy of the retinal pigment epithelium and geographic atrophy of the macula.

PURPOSE: Little information is available on the long-term course of pattern dystrophies, although some older individuals have been observed with macular atrophy. We sought to evaluate the evolution of symptoms, fundus changes, and physiologic findings by re-examining a family with pattern dystrophy after 20 years. METHODS: Four patients of seven initially examined were reevaluated 20 years later; two additional affected family members over age 60 were studied for the first time. Patients' current ages ranged from 38 to 73 years. Comprehensive ophthalmic examinations were supplemented with fluorescein angiography, dark adaptometry, color vision, electroretinography, and electrooculography. RESULTS: During the 20-year interval, visual acuity remained stable and 20/40 or better in all patients. One 62-year-old patient developed paracentral scotomas. All fundi showed evolution of pigmentary changes and increasing atrophy of pigment epithelium and choriocapillaris in the macula. Electro-oculograms were originally subnormal in all patients and changed very little. Electroretinograms, initially normal in two patients, became borderline or mildly subnormal and slightly reduced in the two patients first examined after age 60. CONCLUSIONS: Pattern dystrophy in this family was associated with minimal diminution of visual function during a 20-year interval. However, there was electroretinographic evidence of mild diffuse photoreceptor damage in the older patients, and geographic macular atrophy was prominent (suggesting a risk of vision loss in old age). Some cases of atrophic, age-related macular degeneration may represent an evolution of pattern dystrophy.

Adult↗
PubMed1996

An experimental model of retinal pigment epithelial and neurosensory serous detachment.

PURPOSE: The authors document an animal model of retinal pigment epithelial (RPE) detachments. METHODS: N-ethylmaleimide (NEM) and sodium iodate (sulfhydryl-alkylating agents) were injected into the vitreous of Dutch pigmented rabbits. Subretinal fluid samples were withdrawn 0.5 and 3 hours after NEM injections and analyzed for albumin content by gel electrophoresis. Selected eyes were examined histologically. RESULTS: Injections of 9.2 micrograms NEM caused wrinkling of the retina within 15 minutes, at which time fluorescein angiography revealed multifocal RPE detachments. At this stage, histologic sections showed moderate choroidal edema and RPE detachment. Elevated retinal detachments developed over the next 15 to 25 minutes. Histologic sections showed massive choroidal edema and RPE fragmentation. The albumin concentration of subretinal fluid rose from 60% of serum level at 30 minutes after NEM to 80% after 3 hours. Sodium iodate did not cause choroidal edema or RPE detachment. CONCLUSION: In rabbits, intravitreal NEM causes the rapid appearance of choroidal edema and RPE detachment, followed by serous retinal detachment. The initial effect probably is caused by an alteration of choroidal vascular permeability. The relationship of these effects to sulfhydryl alkylation is unclear because sodium iodate failed to produce RPE detachments. N-ethylmaleimide effects may model aspects of clinical RPE and serous retinal detachments.

Animals↗
PubMed1996

When vitreous enters the subretinal space. Implications for subretinal fluid protein.

PURPOSE: Vitreous enters the subretinal space in rhegmatogenous detachments, but the protein concentration in subretinal fluid from clinical detachments is much higher than in vitreous. These experiments were designed to study short-term changes in subretinal albumin concentration after vitreous enters the subretinal space. METHODS: Retinal detachments were made in Dutch rabbits by injecting autologous liquefied vitreous (albumin concentration 244.11 micrograms/ml) into the subretinal space through a micropipette. Subretinal and vitreous fluid samples were withdrawn 0 to 4 hours later and analyzed for albumin concentration (by gel electrophoresis) and osmolality. The authors also made detachments with Hanks' balanced salt solution containing an approximate vitreal level (294.8 micrograms/ml) of fluorescein isothiocyanate albumin. RESULTS: When the authors made detachments using autologous liquefied vitreous, the subretinal albumin concentration increased to 333.3 micrograms/ml 4 hours after detachment, by which time the detachment volume had fallen to 65% of its initial level. The total amount of albumin in the subretinal space did not change significantly. Subretinal fluid osmolality remained within the range of 292 to 294 mOsm/kg despite the steady absorption of fluid from the detachment. The results were essentially the same when detachments were made with saline and fluorescein isothiocyanate albumin rather than vitreous itself. CONCLUSIONS: The subretinal concentration of albumin increases as water in subretinal fluid is absorbed across the retinal pigment epithelium. If liquefied vitreous continues to enter the subretinal space, as occurs in clinical cases of rhegmatogenous retinal detachment, this mechanism may cause albumin to accumulate.

Absorption↗
PubMed1996

The source of fluid and protein in serous retinal detachments.

PURPOSE: To investigate the source and protein content of sub-retinal fluid in self-forming experimental serous retinal detachments. METHODS: Detachments were induced in Dutch rabbit eyes using rose bengal photosensitization to cause choriocapillaris injury and thrombosis. Serous detachments formed spontaneously within the next 24 h. Subretinal fluid was withdrawn 2, 8 and 24 hrs after photosensitization, and was analyzed for osmolality and albumin content by gel electrophoresis. RESULTS: The albumin concentration in the subretinal fluid of light-induced detachments was 68% of serum level at 3 h after light damage, and rose close to serum level by 24 h. The osmolality of subretinal fluid 24 h after light damage was essentially the same as serum and vitreous fluid. CONCLUSIONS: The subretinal protein and fluid in light-induced detachments in the central retina of the rabbit must come from the choroid, since there are no intrinsic retinal blood vessels in that region of the fundus. These data demonstrate that serous retinal detachments can form from choroidal fluid.

Albumins↗
PubMed1995

The metabolic dependency of retinal adhesion in rabbit and primate.

OBJECTIVE: To determine the oxygen and glucose dependency of retinal adhesion in primate and rabbit. METHODS: Experiments were performed on Dutch rabbits and monkeys. Retinal adhesiveness was measured by peeling the retina from the retinal pigment epithelium in vitro, under different conditions of PO2 and glucose supply, and by observing the amount of adherent pigment. In vivo ischemia was produced by raising the intraocular pressure. RESULTS: Retinal adhesion failed quickly at low oxygen tensions, but a well-oxygenated solution preserved strong retinal adhesion in vitro for 15 to 20 minutes in rabbit tissue and up to 50 minutes in primate tissue. Ischemic adhesive failure was reversible on raising the PO2. Glucose levels did not affect adhesiveness. Ischemia in vivo for more than 1 minute caused rabbit retina to lose its adhesiveness. CONCLUSIONS: Retinal adhesion is continually and reversibly dependent on oxygenation, and probably on aerobic metabolism. Primate tissue is more resistant to metabolic adhesive failure than is rabbit tissue, but the metabolic requirements appear qualitatively similar.

Adhesiveness↗
PubMed1995

The interphotoreceptor matrix mediates primate retinal adhesion.

OBJECTIVE: To assess the participation of cone matrix sheaths, which are domains of the cone photoreceptor-associated interphotoreceptor matrix that extend from the neural retina to the surface of the retinal pigment epithelium (RPE), in retinal adhesion. METHODS: Monkey and human retinas were partially peeled from the RPE, and the tissues were examined by lectin histochemistry to determine the effects of physical separation on the cone matrix sheath. RESULTS: A firm attachment of cone matrix sheaths to both the RPE and the neural retina that was strong enough to cause detachment of sheets of RPE cells from Bruch's membrane or tearing of the sheaths as a result of retinal peeling was observed. Cone matrix sheaths can stretch considerably and contract following tearing. Their integrity was compromised rapidly after the first postmortem minute. CONCLUSION: Cone matrix sheath glycoconjugates are likely to play a major role in mediating retinal adhesion by forming a molecular bridge between the neural retina and the RPE.

Adult↗
PubMed1995

An updated standard for clinical electroretinography.

The value of the electroretinogram (ERG) in clinical practice depends in part on its consistency and the ability to compare results with other laboratories and the literature. These issues were addressed by the publication of the International Standard for Clinical Electroretinography in 1989. This Standard provided technical information and defined a core of basic test procedures and test responses (Figure) to ensure that ERGs performed worldwide would be equivalent for clinical and research purposes. Most major laboratories now subscribe to the tenets of the Standard, and it should be noted that the Standard does not limit laboratories from doing additional specialized tests (beyond the recommendations) for either clinical purposes or research. Since science and medicine are not static, the original Standard mandated revision every 4 years by the International Society for Clinical Electrophysiology of Vision. The first revision, titled "Standard for Clinical Electrophysiology (1994 Update)," has just been published, and it contains changes and new provisions that should be reviewed carefully by those who perform ERGs. The major changes and additions in the updated ERG Standard are as follows.

Adult↗
PubMed1995

Cytochalasin D reversibly weakens retinal adhesiveness.

This study asks whether retinal adhesiveness is affected by cytochalasin D, a drug that is known to alter the apical morphology of the retinal pigment epithelium (RPE). Cytochalasin D was injected intravitreally in Dutch rabbits and retinal adhesiveness measured 0.5 to 72 h later by two methods: in vitro peeling of the retina from retinal pigment epithelium to observe the amount of adherent pigment, and in vivo measurement of the pressure needed to achieve retinal separation. Electroretinograms were recorded, and RPE apical morphology was examined by scanning electron microscopy. The injection of 60 microM cytochalasin D caused in vitro retinal adhesiveness to fall within 3 h to 10% of normal although the electroretinogram (a, b, and c-waves) remained normal. Smaller doses of cytochalasin D had a lesser effect. The RPE apical surface at 3 h showed large bullet-like microvilli, swollen cone sheaths, and an absence of filamentous microvilli. The severity of these changes was dose-related. At 72 h after cytochalasin D, retinal adhesiveness had largely recovered, and RPE apical morphology appeared normal again. Thus, cytochalasin D weakens retinal adhesiveness acutely but reversibly, and both the initial effect and recovery correlate with changes in RPE microvillar morphology. This suggests that actin microfilaments may be involved in mechanisms of retinal adhesion.

Adhesiveness↗
PubMed1995

Post-ischemia ERG recovery is influenced by temperature.

In experimental work on retinal ischemia and its medical management, we have been disturbed by the large variations in the electroetinogram (ERG) recovery of rabbit eyes subjected to similar degrees of ischemia. We investigated whether body temperature might be one of the critical factors. We studied pigmented Dutch rabbits that had been subjected to 60 min of ocular ischemia followed by 4 h of reperfusion at different body temperatures. Ischemia was produced by cannulating the anterior chamber and raising the intraocular pressure. Scotopic ERGs and rectal temperatures were recorded at regular intervals. Rabbits with a subnormal mean temperature of 35.5-37.7 degrees C throughout the experiment showed mean a- and b-wave recoveries of 131.52% and 107.68% of preischemic values after 4 h reperfusion. At temperatures between 37.8-38.9 degrees C, the a- and b-waves only recovered to 88.43% and 32.0% respectively. Even small degrees of cooling greatly enhanced post-ischemic ERG recovery. This may explain some of the variations in ERG recovery that have been reported in the literature. We suggest that body temperature should be tightly controlled between 37.8 and 38.9 degrees C during ischemia experiments to stabilize results and minimize errors in judging therapeutic effects. Retinal cooling may be a means to protect the retina against ischemic damage in clinical situations.

Animals↗
PubMed1995

Albumin movement out of the subretinal space after experimental retinal detachment.

PURPOSE: The subretinal fluid of serous retinal detachments contains protein, but little is known about its origin and fate. The authors designed experiments to study the rate and route of albumin movement out of the subretinal space. METHODS: Experimental retinal detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution containing serum levels (approximately 30 mg/ml) of fluorescein isothiocyanate (FITC) albumin into the subretinal space through a micropipette. Subretinal, vitreous, and serum fluid samples were withdrawn 0 to 4 hours later through a similar micropipette and were analyzed for osmolality, FITC albumin content (by fluorophotometry) and FITC+native albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). RESULTS: Albumin injected into the subretinal fluid diffused steadily into the vitreous, and its concentration decreased by approximately 5% per hour. This rate was unaffected by RPE damage. Albumin did not move into the bloodstream unless the RPE was damaged with sodium iodate, and then it crossed the RPE at approximately 25% of the rate at which it moved into the vitreous. Subretinal fluid osmolality remained within the range of 293 to 294 mOsm/kg despite protein movement and the continual absorption of fluid from the detachments. CONCLUSIONS: These results show that albumin in the subretinal space diffuses readily into the vitreous, and subretinal osmolality changes are rapidly equilibrated with the vitreous. Albumin does not cross normal RPE, and it crosses iodate-damaged RPE more slowly than it crosses retina. Thus, there must be a constant supply of albumin if high subretinal concentrations are to be sustained in clinical serous detachments.

Animals↗
PubMed1994

Conditions necessary for the formation of serous detachment. Experimental evidence from the cat.

OBJECTIVE: To evaluate experimentally the conditions necessary for the formation of serous detachments. METHODS: Selective injury to the retinal pigment epithelium (RPE) and choriocapillaris was produced in cats using weak laser burns and intense diffuse light, with or without photosensitization with rose bengal. The fundi were analyzed by observation, fluorescein angiography, and histologic examination. RESULTS: Injuring the RPE alone did not cause detachments. Focal injury to the RPE and choriocapillaris caused moderate detachment only when an area surrounding the focal leakage site had been subjected to light damage. Diffuse injury to the RPE and choriocapillaris caused broader detachments. CONCLUSIONS: Three conditions are necessary for serous detachments to form: (1) a source of fluid pressure, (2) a defect in the blood-retinal barrier (entry site), and (3) an area of impaired fluid transport beyond the site of leakage (if fluid is to accumulate over a broader area).

Animals↗
PubMed1994

Sequential recording of photic and nonphotic electro-oculogram responses in patients with extensive extramacular drusen.

At present, no clinical electrophysiologic test defines dysfunction of the retinal pigment epithelium. We studied four electrophysiologic responses of the retinal pigment epithelium to compare results from three normal subjects with those from three patients with a diffuse retinal pigment epithelial disorder, extramacular drusen. We recorded the fast oscillation, hyperosmolarity response, acetazolamide response, and light peak by means of a clinical protocol in which these could be elicited consecutively. We found no significant differences between the normal subjects and patients with drusen for any of the four responses. These results suggest that retinal pigment epithelial electrophysiologic function is well maintained despite the widespread physical abnormalities of the retinal pigment epithelium in extramacular drusen. This combined test was well tolerated and may prove useful in characterizing other diseases involving the retinal pigment epithelium.

Acetazolamide↗
PubMed1994

Effect of methazolamide on chronic macular edema in patients with retinitis pigmentosa.

PURPOSE: To determine the effectiveness of methazolamide for improving visual acuity and macular edema in patients with retinitis pigmentosa. METHODS: Seventeen subjects with retinitis pigmentosa and chronic macular edema participated in a prospective, placebo-controlled, double-masked, crossover design study in which either methazolamide or a placebo was taken for 3 weeks. Visual acuity, fluorescein angiograms, and subjective impressions were obtained at baseline and after 3 weeks of treatment with each substance. A subgroup of subjects were enrolled in a more extended period of methazolamide treatment for an additional 3 months. RESULTS: Methazolamide resulted in the improvement of angiographic macular edema in 9 of 17 subjects. As a group, visual acuity statistically improved with methazolamide. However, improvement in at least one eye, of between two and four lines more than while taking placebo, occurred in only three (undilated pupils) or four (dilated pupils) subjects. Subjective improvement during treatment with methazolamide but not placebo occurred in only one subject. An extended period of methazolamide treatment for an additional 3 months in a subgroup of patients did not result in additional beneficial effects on visual acuity. In fact, a partial rebound in the extent of macular edema was found. CONCLUSIONS: Although angiographic improvement of macular edema can occur in patients with retinitis pigmentosa treated with methazolamide, notable (between 3 and 4 lines) or even moderate (between 2 and 3 lines) visual acuity improvement was seen in relatively few patients. When methazolamide was administered in a placebo-controlled fashion, subjective improvement in visual function also was not readily apparent. A more substantial subjective improvement in visual function had occurred with the use of acetazolamide in five of six subjects who also had participated in a previous treatment trial with the use of acetazolamide.

Adolescent↗
PubMed1994

Retinal adhesiveness in surgically enucleated human eyes.

PURPOSE: Retinal adhesion in rabbits and monkeys has been shown to involve the interphotoreceptor matrix and depend on environmental factors, such as temperature, pH, and calcium concentration. This study was designed to see whether these same factors modulate retinal adhesiveness in humans. METHODS: Four surgically enucleated human eyes were studied. Strips of eyecup were placed in experimental baths shortly after enucleation to evaluate environmental conditions. Retinal adhesive strength was quantified by the amount of retinal pigment epithelial pigment adherent to retina peeled from strips of eyecup. Cone and rod sheaths of the interphotoreceptor matrix were studied by microscopic examination of samples stained with the lectins peanut and wheat germ agglutinin. RESULTS: Retinal adhesiveness fell to 0 approximately 40 minutes after enucleation. Adhesive strength was maintained by cold temperature and was weakened by low pH or low calcium in the bath. Cone and rod matrix sheaths became stretched (indicating a bond) as outer segments and retinal pigment epithelium were peeled apart. CONCLUSION: Retinal adhesion in humans appears to involve similar mechanisms as in rabbits and monkeys.

Adhesiveness↗
PubMed1994

The rate and source of albumin entry into saline-filled experimental retinal detachments.

PURPOSE: To investigate the rate and source of albumin entry into experimental nonrhegmatogenous detachments. METHODS: Detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution into the subretinal space through a micropipette. Subretinal fluid was withdrawn 0 to 4 hours later through a similar micropipette and analyzed for osmolality and albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). In some rabbits fluorescein isothiocyanate albumin (FITC-albumin) was injected intravitreally or intravenously to measure its entry into the subretinal fluid by fluorophotometry. Results from 4 to 8 eyes were averaged for each data point. RESULTS: The albumin concentration and total amount of albumin in the subretinal fluid increased steadily over 4 hours in retinal detachments initially filled with Hanks' solution. Pretreating rabbits with sodium iodate injection resulted in a 50-fold increase in the rate of albumin entry, although the levels were still low relative to those of serum. Intravitreal FITC-albumin entered the subretinal fluid at a rate independent of sodium iodate damage, but intravenous FITC-albumin only entered the subretinal space after RPE damage. Subretinal fluid osmolality remained within the range of 291 to 294 mOsm/kg, irrespective of sodium iodate damage or differences in the rate of fluid absorption. CONCLUSIONS: These results indicate that albumin can diffuse into the rabbit subretinal space from both vitreous and bloodstream, although entry from serum requires damage to the RPE. Subretinal fluid appears to be transported actively (control eyes) or passively (iodate-damaged eyes) out of the subretinal space, despite albumin entry and without major osmolar shifts.

Animals↗
PubMed1994

Electroretinogram recovery in the rabbit after repetitive short-term ischemia in light and dark.

PURPOSE: To determine the time course and reproducibility of electroretinogram recovery after short-term (5- to 20-minute) retinal ischemia in the light and in the dark. METHODS: Electroretinogram recovery was measured in Dutch rabbits after 5-, 10-, or 20-minute episodes of ocular ischemia, repeated three times at 1-hour intervals. Results were compared under light- and dark-adapted conditions. RESULTS: The rate of b-wave recovery was highly reproducible after repetitive ischemic insults in the same eye. The rate of b-wave recovery varied in proportion to the duration of ischemia but generally reached 100% of preischemic levels within 45 to 60 minutes. Recovery was slower under dark-adapted conditions than under light-adapted conditions, and 10 minutes of ischemia appeared to be a critical duration to maximize light- and dark-adapted metabolic differences. CONCLUSIONS: Because of the speed and reproducibility of electroretinogram recovery, the use of short-term ischemic episodes may facilitate studies on the pharmacologic therapy of retinal ischemia. It remains to be determined, however, whether the retinal effects of short-term ischemia are mediated by the same mechanisms as the effects of longer-term ischemia.

Animals↗